A Facile Method for the Synthesis of Dihydrofuranonaphthoquinones, Furanonaphthoquinones, and Benzofuranonaphthoquinones

Article abstract of DOI:10.1081/SCC-120026354

An efficient synthesis of dihydrofuranonaphthoquinone, furanonaphthoquinone, and benzonaphthoquinone derivatives has been carried out starting from 2-hydroxy-1,4-naphthoquinone and a variety of vinyl sulfides in moderate yields.

Full text of DOI:10.1081/SCC-120026354

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A Facile Method for the Synthesis
of Dihydrofuranonaphthoquinones,
Furanonaphthoquinones, and
Benzofuranonaphthoquinones
a
a
Yong Rok Lee & Byung So Kim
a
School of Chemical Engineering and Technology , College of Engineering , Yeungnam
University , Kyongsan, Korea
Published online: 16 Aug 2006.
To cite this article: Yong Rok Lee & Byung So Kim (2003) A Facile Method for the Synthesis of Dihydrofuranonaphthoquinones,
Furanonaphthoquinones, and Benzofuranonaphthoquinones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:23, 4123-4135, DOI: 10.1081/SCC-120026354
To link to this article: http://dx.doi.org/10.1081/SCC-120026354
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 23, pp. 4123–4135, 2003
A Facile Method for the Synthesis of
Dihydrofuranonaphthoquinones,
Furanonaphthoquinones, and
Benzofuranonaphthoquinones
Yong Rok Lee* and Byung So Kim
School of Chemical Engineering and Technology,
College of Engineering, Yeungnam University,
Kyongsan, Korea
ABSTRACT
An efficient synthesis of dihydrofuranonaphthoquinone, furano-
naphthoquinone, and benzonaphthoquinone derivatives has been
carried out starting from 2-hydroxy-1,4-naphthoquinone and a
variety of vinyl sulfides in moderate yields.
Key Words: Dihydrofuranonaphthoquinones; Furanonaphthoqui-
nones; Benzofuranonaphthoquinones.
*
Correspondence: Yong Rok Lee, School of Chemical Engineering and
Technology, College of Engineering, Yeungnam University, Kyongsan 712-749
Korea; E-mail: yrlee@yu.ac.kr.
4
123
DOI: 10.1081/SCC-120026354
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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4
124
Lee and Kim
Dihydrofuranonaphthoquinone and furanonaphthoquinone deriva-
[
tives are widely distributed in nature and they have shown a number of
1]
[
biological activities such as antileukemic activity, in vitro cytotoxicity
2]
[
against KB, K562, and P388 cells, and in vitro antiprotozoan activity
3]
[
against Trypanosoma cruzi. They have also been used in medicine
4]
for many years in North and South America for anticancer, antifungal,
[
antibacterial, and anti-inflammatory activities.
5]
Benzofuranonaphthoquinone derivatives are also biologically and
pharmacologically interesting compounds. They have recently been
become synthetic targets due to their significant biological activities
such as antipruritic, antitumor, antineoplastic ellipticine, and topo
[
6]
II-mediate DNA cleavage.
Although several synthetic approaches to the linearly fused dihydro-
furanonaphthoquinone, furanonaphthoquinone, and benzofuranonaph-
thoquinone derivatives have been reported, their synthetic exploitation
has been limited because of their complex reaction sequences with
[7]
many reaction steps. In particular, no synthetic methods for the
angularly fused benzofuranonaphthoquinone derivatives have been
reported to date.
Recently, we have reviewed the CAN-mediated oxidative cycloaddi-
[
tion of 1,3-dicarbonyl compounds with conjugated compounds.
8]
Following our studies based on the CAN-mediated oxidative cycloaddi-
tion, we have expanded this work to the synthesis of a variety of medium-
and large-sized ring substituted dihydrofuranonaphthoquinones
with sulfide groups. We describe herein a facile and efficient synthesis
of linearly and angularly fused dihydrofuranonaphthoquinone,
furanonaphthoquinone, and benzofuranonaphthoquinone derivatives.
The strategy begins with the reaction of 2-hydroxy-1,4-naphthoqui-
none (1) and vinyl sulfides 2–7 (Fig. 1) in the presence of 2.2 equiv. of
ceric(IV) ammonoum nitrate and an excess amount of NaHCO in THF
3
R
O
O
SPh
SPh
SPh
2
3 R= H
R= Me
5
4
OH
1
SPh
SPh
6
7
Figure 1.

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Dihydrofuranonaphthoquinones
4125
or acetonitrile. Reaction of 1 with vinyl sulfide 3 (2-fold excess) at room
temperature for 6 h in THF afforded dihydrofuranonaphthoquinones 8
(
45%) and 9 (23%), whereas reaction in acetonitrile gave products in 32
and 34% yields as a mixture of linear and angular isomers (Sch. 1).
Interestingly, there is a moderate solvent dependence in yield and stereo-
selectivity. The mixture was easily separated by column chromatography
and two isomers were assigned by their spectroscopic analysis. The clear
assignments come from the IR carbonyl absorptions at 1680 and
ꢀ
1
ꢀ1
1651 cm for the two carbonyls in 8, and at 1698 and 1653 cm in 9.
The stereochemistry of 8 and 9 is assigned as cis from the spectral analysis
[
9]
and by analogy with data that had been reported earlier.
In order to extend the utility of these oxidative cycloadditions,
additional reactions of 1 with other sulfides in THF or acetonitrile
were next investigated. Reaction of 1 with vinyl sulfide 2 in THF afforded
adducts 10 and 11 in 40 and 19% yields. In vinyl sulfides 6 and 7 with
medium- and large-sized ring systems, cycloaddition was successful.
Treatment with 6 in acetonitrile for 6 h afforded cycloadducts 16 and
1
1
7 in 38 and 41% yield, whereas reaction with 7 gave products 18 and
9 in 33 and 44% yields. These reactions provide a rapid synthetic route
to the preparation of dihydrofuranonaphthoquinone derivatives that
vary in ring size. The results are summarized in Table 1.
Next, these cycloadducts can be elaborated toward biologically
interesting materials such as furanonaphthoquinones and benzofurano-
naphthoquinones. For example, linear and angular dihydrofurano-
naphthoquinones with phenyl sulfide groups can be readily converted
to furanonaphthoquinones by elimination of phenyl sulfide. Treatment
of 18 with mCPBA in CH Cl at room temperature for 12 h afforded
2
2
the corresponding sulfoxide, which upon refluxing for 6 h in m-xylene
delivered furanonaphthoquinone 20 in 75% yield (Sch. 2). When
PhS
O
O
O
O
H
SPh
3
H
+
O
SPh
OH Ce(NH4)2(NO3)6
O
O
8
9
O
1
product
solvent
8
9
THF
acetonitrile
45%
32%
23%
34%
Scheme 1.

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4
126
Table 1. Reaction of 2-hydroxy-1,4-naphthoquinone (1) with vinyl sulfides.
-Hydroxy-1,4- Vinyl
Lee and Kim
2
naphthoquinone sulphide
Solvent
Product (yield)
O
O
H
PhS
O
2
H
O
O
SPh
OH
O
5
O
10 (40%)
1
1 (19%)
1
O
PhS
O
4
5
6
7
O
H
H
THF
H
O
O
SPh
O
O
12 (43%)
1
3 (19%)
O
PhS
O
THF
O
SPh
14 (44%)
H
O
O
O
1
5 (23%)
O
PhS
O
acetonitrile
H
O
SPh
H
O
O
1
6 (38%)
1
7 (41%)
O
acetonitrile
O
PhS
O
H
O
SPh
H
O
18 (33%)
O
O
19 (44%)
O
O
i) mCPBA
CH Cl
O
2
2
ii) xylene
heat
O
SPh
O
75%
O
18
20
Scheme 2.

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Dihydrofuranonaphthoquinones
4127
O
O
O
O
O
70%
O
O
8
23
0%
21
22
7
4%
O
O
O
O
O
O
72%
O
71%
O
68%
24
25
O
26
O
O
Figure 2.
R
R
O
O
O
O
Pd/C
Ph O
2
O
O
reflux
2
2
1 R=H
27 R=H 42%
2 R=CH3
28 R=CH3 40%
Scheme 3.
angularly fused dihydrofuranonaphthoquinone 9 was treated under the
same reaction conditions, furanonaphthoquinone 24 was obtained in
72% yield. The other similar results are collected in Fig. 2.
As another application of this methodology, conversion to pharma-
cologically interesting benzofuranonaphthoquinone derivatives was next
examined. The strategy begins by dehydrogenation of obtained linear and
angular furanonaphthoquinones derivatives. Treatment of 21 and 22 with
Pd/C for 5 h in refluxing phenyl ether afforded benzofuranonaphthoqui-
nones 27 and 28 in 42 and 40% yields, respectively (Sch. 3). Similarly, the
angularly fused furanonaphthoquinone 24 was also transformed into
benzofuranonaphthoquinone 29 (40%) when subjected to the same
reaction conditions (Sch. 4). The assignment of 27–29 is easily confirmed
1
by spectroscopic analyses, primarily NMR. The H NMR spectra of
27–29 exhibited aromatic protons associated with the new aromatic ring.
In conclusion, a concise synthetic route to linear and angular
dihydrofuranonaphthoquinone products has been developed from readily
available 2-hydroxy-1,4-napthoquinone (1) and vinyl sulfides 2–6. As

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128
Lee and Kim
O
O
Pd/C
Ph O
reflux
2
O
O
O
O
4
0%
24
2
9
Scheme 4.
an application of this methodology, the products can be further
converted to linearly and angularly fused furanonaphthoquinone and
benzofuranonaphthoquinone derivatives.
EXPERIMENTAL
All experiments were carried out under a nitrogen atmosphere.
Merck precoated silica gel plates (Art. 5554) with fluorescent indicator
were used for analytical TLC. Flash column chromatography was
performed using silica gel 9385 (Merck). Melting points were determined
in capillary tubes on a Fisher–Johns apparatus and are uncorrected.
1
H NMR spectra were recorded on a Bruker Model ARX (300 MHz)
1
3
spectrometer. C NMR spectra were recorded on a Varian Model
Unity INOVA (125 MHz) spectrometer at the Korea Basic Science
Institute (Daegu). Infrared spectra were recorded on a Jasco FTIR
5300 spectrophotometer. High resolution mass spectra were obtained
with a JEOL JMS-700 spectrometer at the Korea Basic Science
Institute (Daegu). Elementary analyses were performed by the Korea
Basic Science Institute (Daegu).
General Procedure for Synthesis of
Dihydrofuranonaphthoquinones
To a solution of 2-hydroxy-1,4-naphthoquinone (1) (1.0 mmol) and
vinyl sulfide (2.0 mmol) in THF (20 mL) or acetonitrile (20 mmol) was
added CAN (1.206 g, 2.2 mmol) and NaHCO (420 mg, 5.0 mmol) at
3
room temperature. The reaction mixture was stirred for 6 h at room
temperature in THF or acetonitrle. The mixture was diluted with water
and extracted with ethyl acetate (3 ꢁ 50 mL). The combined organic
extracts were washed with brine, dried (MgSO ), and evaporated under
4

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Dihydrofuranonaphthoquinones
4129
reduced pressure to give the residue. The residue was purified by flash
column chromatography on sillica gel to give product.
4
a-Phenylsulfanyl-1,2,3,4,4a,11b-hexahydro-benzo[b]naphtho[2,3-
d]furan-6,11-dione (8) and 10a-phenylsulfanyl-6b,7,8,9,10,10a-hexa-
hydro-benzo[b]naphtho[2,1-d]furan-5,6-dione (9). Reaction of 2-
hydroxy-1,4-naphthoquinone (1) (174 mg, 1 mmol) with vinyl sulfide
3
(381 mg, 2 mmol) in THF (20 mL) afforded 8 (163 mg, 45%) and 9
ꢂ
1
(83 mg, 23%) as a mixture. 8. M.p.: 94–95 C. H NMR (300 MHz,
CDCl ) ꢀ: 8.07–7.97 (2H, m), 7.72–7.62 (2H, m), 7.60–7.54 (2H, m),
3
7
1
1
1
1
1
.30–7.27 (3H, m), 3.42 (1H, dd, J ¼ 6.4, 6.3 Hz), 2.18–1.97 (2H, m),
1
3
.69–1.47 (6H, m). C NMR (75 MHz, CDCl ) ꢀ: 181.70, 177.75,
3
57.73, 136.15, 133.97, 132.88, 131.43, 129.54, 129.40, 129.23, 129.08,
28.97, 128.80, 128.16, 125.96, 125.78, 103.09, 45.94, 31.53, 25.49,
9.11, 18.98. IR (KBr): 3063, 2944, 2865, 1680, 1651, 1624, 1595,
ꢀ1
476, 1439, 1387, 1360, 1248, 1202, 1161, 951, 901, 849 cm . HRMS
þ
m/z (M ) Calcd. for C H O S: 362.0977. Found: 362.0979. Anal.
2
2
18
3
calcd. for C H O S: C, 72.90; H, 5.01; S, 8.85. Found: C, 73.02. H,
2
2
18
3
ꢂ
.95; S, 8.46; 9. M.p.: 118–120 C. H NMR (300 MHz, CDCl ) ꢀ: 8.05
3
1
4
(
(
(
1H, d, J ¼ 8.2 Hz), 7.68–7.66 (2H, m), 7.57–7.52 (3H, m), 7.35–7.15
3H, m), 3.41 (1H, dd, J ¼ 6.1, 6.0 Hz), 2.09–1.96 (2H, m), 1.82–1.44
1
3
6H, m). C NMR (75 MHz, CDCl ) ꢀ: 180.92, 174.91, 167.60, 136.21,
3
1
1
34.57, 131.84, 130.66, 129.61, 129.48, 129.42, 129.29, 128.98, 128.82,
27.56, 124.35, 119.71, 104.43, 45.14, 31.45, 24.27, 18.70, 18.34. IR
(
KBr): 3071, 2942, 1698, 1653, 1620, 1572, 1400, 1350, 1254, 1215,
163, 1055, 1022, 986, 862 cm . HRMS m/z (M ) Calcd. for
ꢀ þ
1
1
C H O S: 362.0977. Found: 362.0980. Anal. calcd. for C H O S:
2
2
18
3
22 18
3
C, 72.90; H, 5.01; S, 8.85. Found: C, 73.05; H, 5.04. S, 8.73.
0a-Phenylsulfanyl-2,3,3a,10a-tetrahydro-1H-10-oxa-pentaleno[1,2-
b]naphthalene-4,9-dione (10) and 9a-phenylsulfanyl-7,8,9,9a-tetrahydro-
1
6
2
2
bH-10-oxa-pentaleno[2,1-a]naphthalene-5,6-dione (11). Reaction of
-hydroxy-1,4-naphthoquinone (1) (174 mg, 1 mmol) with vinyl sulfide
(353 mg, 2 mmol) in THF (20 mL) afforded 10 (139 mg, 40%) and 11
ꢂ
1
(66 mg, 19%) as a mixture. 10. M.p.: 93–94 C. H NMR (300 MHz,
CDCl ) ꢀ: 8.03–8.01 (1H, m), 7.99–7.94 (1H, m), 7.69–7.59 (4H, m),
3
7
2
3
1
.26–7.22 (3H, m), 3.82 (1H, d, J ¼ 9.0, 2.6 Hz), 2.44–2.35 (1H, m),
.21–2.02 (2H, m), 2.01–1.80 (2H, m), 1.74–1.59 (1H, m). IR (KBr):
054, 2957, 2866, 1690, 1647, 1628, 1595, 1572, 1391, 1364, 1252,
ꢀ
1
þ
204, 1071, 966, 936, 880 cm . HRMS m/z (M ) Calcd. for
ꢂ
C H O S: 348.0820. Found: 348.0818. 11. M.p.: 108–110 C.
2
1
16
3
1
H NMR (300 MHz, CDCl ) ꢀ: 8.00 (1H, d, J ¼ 7.9 Hz), 7.68–7.65 (2H,
3
m), 7.59–7.54 (3H, m), 7.28–7.17 (3H, m), 3.77 (1H, dd, J ¼ 8.4,
.8 Hz), 2.15–2.05 (2H, m), 1.94–1.8 (2H, m), 1.70–1.55 (2H, m). IR
1

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130
Lee and Kim
(
KBr): 3057, 2963, 1701, 1653, 1620, 1574, 1439, 1402, 1346, 1221,
ꢀ þ
082, 912, 885 cm . HRMS m/z (M ) Calcd. for C H O S:
21 16 3
1
1
3
48.0820. Found: 348.0821.
-Methyl-4a-phenylsulfanyl-1,2,3,4,4a,11b-hexahydro-benzo[b]naphtho
2,3-d]furan-6,11-dione (12) and 8-Methyl-10a-phenylsulfanyl-6b,7,8,9,10,
2
[
10a-hexahydrobenzo[b]naphtho[2,1-d]furan-5,6-dione (13). Reaction of
2-hydroxy-1,4-naphthoquinone (1) (174 mg, 1 mmol) with vinyl sulfide 4
(
(
409 mg, 2 mmol) in THF (20 mL) afforded 12 (162 mg, 43%) and 13
ꢂ
1
72 mg, 19%) as a mixture. 12. M.p.: 91–93 C. H NMR (300 MHz,
CDCl ) ꢀ: 8.07–7.98 (2H, m), 7.71–7.64 (2H, m), 7.60–7.54 (2H, m),
3
7
.32–7.26 (3H, m), 3.54 (1H, dd, J ¼ 6.0, 3.0 Hz), 2.21–2.02 (2H, m),
.68–1.53 (3H, m), 1.26–1.16 (2H, m), 0.94 (3H, d, J ¼ 6.0 Hz).
1
1
3
C NMR (75 MHz, CDCl ) ꢀ: 182.00, 177.67, 158.27, 136.16, 134.05,
3
1
1
32.99, 132.88, 131.45, 129.53, 129.36, 129.07, 128.94, 127.12, 126.20,
25.99, 125.80, 103.26, 45.40, 31.35, 31.20, 27.70, 25.05, 21.88. IR
(
KBr): 3065, 2951, 1682, 1651, 1624, 1595, 1574, 1541, 1385, 1358,
ꢀ þ
1
1267, 1204, 1005, 945, 839 cm . HRMS m/z (M ) Calcd. for
C H O S: 376.1133. Found: 376.1132. Anal. calcd. for C H O S: C,
2
3
20
3
23 20
3
7
1
7
3.38; H, 5.35; S, 8.52. Found: C, 73.14; H, 5.26; S, 8.56. 13. M.p.:
ꢂ
1
51–153 C. H NMR (300 MHz, CDCl ) ꢀ: 8. 04 (1H, d, J ¼ 7.6 Hz),
3
.67–7.64 (2H, m), 7.59–7.50 (3H, m), 7.35–7.26 (3H, m), 3.49 (1H, dd,
J ¼ 6.0, 3.0 Hz), 2.30–2.21 (1H, m), 2.15–2.07 (1H, m), 2.03–1.90 (1H, m),
1
2
8
3
.74–1.60 (2H, m), 1.27–1.86 (2H, m), 0.93 (3H, d, J ¼ 6.0 Hz). IR (KBr):
926, 1701, 1651, 1620, 1589, 1572, 1454, 1399, 1221, 1163, 1067,
ꢀ
1
41 cm . HRMS m/z (M ) Calcd. for C H O S: 376.1133. Found:
þ
2
3
20
3
76.1135. Anal. calcd. for C H O S: C, 73.38; H, 5.35; S, 8.52.
2
3
20
3
Found: C, 73.16; H, 5.29; S, 8.18.
0a-Phenylsulfanyl-6,7,8,9,10,10a-hexahydro-5bH-11-oxa-naphtho
2,3-a]azulene-5,12-dione (14) and 11a-phenylsulfanyl-7,8,9,10,11,11a-
1
[
hexahydro-6bH-12-oxa-naphtho[2,1-a]azulene-5,6-dione (15). Reaction
of 2-hydroxy-1,4-naphthoquinone (1) (174 mg, 1 mmol) with vinyl
sulfide 5 (409 mg, 2 mmol) in THF (20 mL) afforded 14 (166 mg, 44%)
ꢂ
1
and 15 (87 mg, 23%) as a mixture. 14. M.p.: 135–137 C. H NMR
(
(
(
300 MHz, CDCl ) ꢀ: 8.09–8.02 (2H, m), 7.73–7.63 (2H, m), 7.58–7.54
3
2H, m), 7.32–7.28 (3H, m), 3.50 (1H, dd, J ¼ 9.5, 2.9 Hz), 2.15–2.03
1
3H, m), 1.79–1.40 (7H, m). C NMR (75 MHz, CDCl ) ꢀ: 181.74,
3
3
1
1
3
1
77.95, 156.52, 136.41, 134.07, 133.06, 132.90, 131.53, 129.83, 129.52,
29.37, 128.96, 128.81, 128.14, 126.16, 125.98, 107.92, 53.21, 35.53,
0.64, 29.35, 28.60, 24.46. IR (KBr): 2932, 1682, 1647, 1624, 1593,
ꢀ1
389, 1366, 1273, 1221, 1206, 1169, 970, 951, 804 cm . HRMS m/z
þ
(M -PhSH) Calcd. for C H O : 266.0943. Found: 266.0945. Anal.
calcd. for C H O S: C, 73.38; H, 5.35; S, 8.52. Found: C, 73.11;
1
7
14
3
2
3
20
3

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Dihydrofuranonaphthoquinones
4131
ꢂ
1
H, 5. 30; S, 8.48. 15. M.p.: 143–145 C. H NMR (300 MHz, CDCl ) ꢀ:
3
8
.06 (1H, d, J ¼ 7.5 Hz), 7.70–7.50 (5H, m), 7.39–7.26 (3H, m), 3.48 (1H,
dd, J ¼ 9.5, 2.9 Hz), 2.13–2.07 (3H, m), 1.88–1.59 (7H, m). IR (KBr):
3
1
067, 2938, 2855, 1698, 1651, 1620, 1589, 1574, 1474, 1443, 1399, 1319,
ꢀ
1
223, 1084, 960, 876 cm . HRMS m/z (M -PhSH) Calcd. for
þ
C H O : 266.0943. Found: 266.0938.
14
1
7
3
Dihydrofuranonaphthoquinones 16 and 17. Reaction of 2-hydroxy-1,4-
naphthoquinone (1) (174 mg, 1 mmol) with vinyl sulfide 6 (437 mg,
2
4
mmol) in THF (20 mL) afforded 16 (148 mg, 38%) and 17 (160 mg,
ꢂ
1
1%) as a mixture. 16. M.p.: 180–181 C. H NMR (300 MHz, CDCl )
3
ꢀ
: 8.08–8.02 (2H, m), 7.71–7.66 (2H, m), 7.56–7.53 (2H, m), 7.29–7.27
3H, m), 3.25 (1H, t, J ¼ 4.9 Hz), 2.06–1.93 (3H, m), 1.71–1.37 (9H, m).
IR (KBr): 3061, 2934, 2851, 1680, 1653, 1609, 1593, 1468, 1441, 1379,
(
ꢀ
1
þ
1350, 1267, 1204, 1161, 1140, 1001, 959, 922 cm . HRMS m/z (M ):
Calcd. for C H O S: 390.1290. Found: 390.1292. 17. M.p.: 167–
2
4
22
3
ꢂ
1
1
68 C. H NMR (300 MHz, CDCl ) ꢀ: 8.03 (1H, dd, J ¼ 7.6 Hz), 7.66–7.50
3
(
1
1
5H, m), 7.30–7.22 (3H, m), 3.29 (1H, d, J ¼ 8,5 Hz), 2.29–1.87 (3H, m),
.76–1.48 (9H, m). IR (KBr): 2916, 2851, 1695, 1651, 1622, 1575, 1489,
ꢀ
1
440, 1398, 1342, 1311, 1224, 1163, 1078, 877 cm . HRMS m/z (M ):
þ
Calcd. for C H O S: 390.1290. Found: 390.1293.
3
2
4
22
Dihydrofuranonaphthoquinones 18 and 19. Reaction of 2-hydroxy-1,4-
naphthoquinone (1) (174 mg, 1 mmol) with vinyl sulfide 7 (549 mg,
2
4
mmol) in THF (20 mL) afforded 18 (147 mg, 33%) and 19 (197 mg,
ꢂ
1
4%) as a mixture. 18. M.p.: 181–183 C. H NMR (300 MHz, CDCl )
3
ꢀ
(
: 8.08–8.02 (2H, m), 7.73–7.63 (2H, m), 7.60–7.55 (2H, m), 7.28–7.26
3H, m), 3.29 (1H, d, J ¼ 8.6 Hz), 2.24–2.08 (2H, m), 1.93–1.30 (18H, m).
IR (KBr): 3067, 2930, 2843, 1682, 1651, 1634, 1593, 1572, 1441, 1385,
ꢀ
1
1
1
1
8
360, 1312, 1385, 1227, 1204, 1163, 951, 908, 868 cm . 19. M.p.:
ꢂ
1
66–167 C. H NMR (300 MHz, CDCl ) ꢀ: 8.04 (1H, dd, J ¼ 7.4,
3
.0 Hz), 7.72–7.50 (5H, m), 7.35–7.17 (3H, m), 3.29 (1H, d, J ¼
1
3
.6 Hz), 2.25–2.12 (2H, m), 1.96–1.21 (18H, m). C NMR (75 MHz,
CDCl ) ꢀ: 180.92, 174.48, 165.15, 136.49, 134.87, 132.06, 131.03,
3
1
1
2
1
30.24, 129.88, 129.69, 129.58, 129.11, 128.94, 127.93, 124.63, 123.42,
09.02, 30.80, 30.69, 30.19, 28.95, 28.76, 28.60, 26.00, 25.81, 25.68,
5.05. IR (KBr): 3063, 2915, 1695, 1651, 1622, 1588, 1576, 1489, 1439,
ꢀ
1
399, 1341, 1312, 1225, 1163, 1042, 1022, 997, 878, 833 cm
.
General Procedure for Synthesis of Furanonaphthoquinones
To a solution of dihydrofuranonaphthoquinones (0.5 mmol) in
dichloromethane (10 mL) was added mCPBA (247 mg, 70%, 1.0 mmol)

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132
Lee and Kim
at room temperature and the reaction mixture was stirred under nitrogen
for 24 h. Saturated aqueous NaHCO3 solution was added, and the
aqueous layer was extracted with dichloromethane (3 ꢁ 30 mL). The
combined organic extracts were washed with brine, dried (MgSO ), and
4
evaporated under reduced pressure to give the residue. The residue
was refluxed for 6 h in m-xylene (10 mL) and then cooled to room
temperature. Evaporation of solvent and purification by flash column
chromatography on sillica gel to give products.
Furanonaphthoquinone 20. Treatment of 18 (223 mg, 0.5 mmol) with
mCPBA (247 mg, 70%, 1.0 mmol) in dichloromethane (10 mL) followed
by refluxing in m-xylene afforded 20 (126 mg, 75%) as a solid. M.p.:
ꢂ
40 C. H NMR (300 MHz, CDCl ) ꢀ: 8.18–8.10 (2H, m), 7.72–7.68
3
1
1
(
1
2H, m), 3.00–2.91 (4H, m), 1.82–1.74 (4H, m), 1.56–1.40 (12H, m).
3
C NMR (75 MHz, CDCl ) ꢀ: 182.42, 173.06, 161.34, 150.74, 133.63,
3
1
2
3
1
3
33.50, 133.36, 132.68, 129.44, 126.70, 126.51, 120.73, 28.17, 28.03,
7.89, 27.75, 27.60, 26.25, 25.61, 25.52, 25.45, 21.30. IR (KBr): 3100,
069, 1672, 1595, 1537, 1454, 1379, 1348, 1294, 1260, 1211, 1194, 1177,
ꢀ
1
þ
157, 1042, 1007, 968, 937 cm . HRMS m/z (M ) Calcd. for C H O :
2
2
24
3
36.1725. Found: 336.1726.
,2,3,4-Tetrahydro-benzo[b]naphtho[2,3-d]furan-6,11-dione (21). Treat-
1
ment of 8 (181 mg, 0.5 mmol) with mCPBA (247 mg, 70%, 1.0 mmol) in
dichloromethane (10 mL) followed by refluxing in m-xylene afforded
ꢂ
1
1 (88 mg, 70%) as a solid. M.p.: 162–164 C. H NMR (300 MHz,
2
CDCl ) ꢀ: 8.19–8.10 (2H, m), 7.73–7.67 (2H, m), 2.82–2.73 (4H, m),
3
1
.95–1.55 (4H, m). C NMR (75 MHz, CDCl ) ꢀ: 181.99, 173.07,
3
1
3
1
1
59.72, 150.98, 133.60, 133.32, 133.16, 132.63, 129.28, 126.65, 126.47,
18.66, 23.49, 22.12, 22.04, 21.19. IR (KBr): 3067, 2940, 2865, 1667,
593, 1537, 1468, 1429, 1379, 1329, 1279, 1236, 1208, 1148, 990, 953,
1
9
ꢀ þ
30. 823 cm . HRMS m/z (M ): Calcd. for C H O : 252.0787.
16 12 3
1
Found: 252.0785.
2-Methyl-1,2,3,4-tetrahydro-benzo[b]naphtha[2,3-d]furan-6,11-dione (22).
Treatment of 12 (188 mg, 0.5 mmol) with mCPBA (247 mg, 70%,
1.0 mmol) in dichloromethane (10 mL) followed by refluxing in
m-xylene afforded 22 (99 mg, 74%) as a solid. M.p.: 109–111 C.
ꢂ
1
H NMR (300 MHz, CDCl ) ꢀ: 8.19–8.10 (2H, m), 7.73–7.63 (2H, m),
3
3
.03–2.96 (1H, m), 2.8–2.70 (3H, m), 2.37–2.28 (2H, m), 2.02–1.86 (2H,
1
3
m), 1.11 (3H, d, J ¼ 6.6 Hz). C NMR (75 MHz, CDCl ) ꢀ: 182.03,
3
1
1
1
73.10, 159.58, 151.29, 133.68, 133.38, 132.64, 129.24, 127.53, 126.70,
26.50, 118.56, 30.15, 29.33, 28.84, 22,98, 20.97. IR (KBr): 2928. 1667,
ꢀ1
593, 1539, 1431, 1377, 1327, 1294, 1238, 1200, 1146, 984, 914 cm
þ
.
HRMS m/z (M ): Calcd. for C H O : 266.0943. Found: 266.0942.
1
7
14
3
Anal. calcd. for C H O : C, 76.68; H, 5.30. Found: C, 76.95. H, 5.31.
7
1
14
3

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Dihydrofuranonaphthoquinones
4133
Furanonaphthoquinone 23. Treatment of 16 (195 mg, 0.5 mmol) with
mCPBA (247 mg, 70%, 1.0 mmol) in dichloromethane (10 mL) followed
by refluxing in m-xylene afforded 23 (112 mg, 80%) as a solid. M.p.:
ꢂ
72 C. H NMR (300 MHz, CDCl ) ꢀ: 8.19–8.10 (2H, m), 7.71–7.68
3
1
1
(
2H, m), 2.78–2.67 (4H, m), 1.84–1.23 (8H, m). IR (KBr): 2928, 2851,
1
1
2
671, 1593, 1539, 1466, 1446, 1373, 1350, 1298, 1254, 1213, 1192, 1146,
ꢀ
1
076, 1022, 982, 941, 916 cm . HRMS m/z (M ) Calcd. for C H O :
þ
1
7
14
3
66.0943. Found: 266.0940.
,8,9,10-Tetrahydrobenzo[b]naphtha[2,1-d ]furan-5,6-dione (24). Treat-
7
ment of 9 (181 mg, 0.5 mmol) with mCPBA (247 mg, 70%, 1.0 mmol) in
dichloromethane (10 mL) followed by refluxing in m-xylene afforded 24
ꢂ
91 mg, 72%) as a solid. M.p.: 212–214 C. H NMR (300 MHz, CDCl ) ꢀ:
3
1
(
8
2
1
9
2
7
.01 (1H, d, J ¼ 7.6 Hz), 7.63–7.53 (2H, m), 7.37 (1H, dd, J ¼ 8.4, 7.6 Hz),
.72–2.64 (4H, m), 1.90–1.84 (2H, m), 1.79–1.67 (2H, m). IR (KBr): 2942,
698, 1667, 1601, 1580, 1549, 1485, 1447, 1360, 1281, 1215, 1148, 1073,
ꢀ
1
þ
01 cm . HRMS m/z (M ) Calcd. for C H O : 252.0787. Found:
3
1
6
12
52.0786. Anal. calcd. for C H O : C, 76.18; H, 4.79. Found: C,
1
6
12
3
6.53; H, 4.88.
Furanonaphthoquinone 25. Treatment of 17 (195 mg, 0.5 mmol) with
mCPBA (247 mg, 70%, 1.0 mmol) in dichloromethane (10 mL) followed
by refluxing in m-xylene afforded 25 (100 mg, 71%) as a solid. M.p.:
ꢂ
1
1
7
1
1
50–151 C. H NMR (300 MHz, CDCl ) ꢀ: 8.00 (1H, d, J ¼ 7.4 Hz),
3
.63–7.51 (2H, m), 7.36 (1H, dd, J ¼ 8.3, 7.4 Hz), 2.89–2.81 (4H, m),
.82–1.71 (4H, m), 1.50–1.38 (4H, m). IR (KBr): 2938, 2851, 1698,
ꢀ1
667, 1578, 1551, 1487, 1458, 1362m 1219, 1146, 901 cm . HRMS m/z
þ
(
M ): Calcd. for C H O : 280.1099. Found: 280.1096.
1
8
16
3
Furanonaphthoquinone 26. Treatment of 19 (223 mg, 0.5 mmol) with
mCPBA (247 mg, 70%, 1.0 mmol) in dichloromethane (10 mL) followed
by refluxing in m-xylene afforded 26 (114 mg, 68%) as a solid. M.p.:
ꢂ
1
1
7
(
45–147 C. H NMR (300 MHz, CDCl ) ꢀ: 7.99 (1H, d, J ¼ 7.3 Hz),
3
.63–7.53 (2H, m), 7.35 (1H, ddd, J ¼ 8.3, 7.3, 1.7 Hz), 2.89–2.81
4H, m), 1.86–1.71 (4H, m), 1.58–1.47 (12H, m). IR (KBr): 2938, 1697,
ꢀ1 þ
1667, 1551, 1458, 1362, 1219, 1146, 909 cm . HRMS m/z (M ) Calcd.
for C H O : 336.1725. Found: 336.1723.
2
2
24
3
Benzo[b]naphtha[2,3-d ]furan-6,11-dione (27). To a stirred solution of
1 (100 mg, 0.4 mmol) in phenyl ether (5 mL) was added Pd/C (100 mg,
0 wt%). The mixture was refluxed for 5 h and cooled to room tempera-
2
1
ture. The suspension was filtered off and inorganic material was washed
with ethyl acetate (50 mL). The solvent was evaporated under reduced
pressure to give the residue. The residue was purified by flash column
chromatography on silica gel to give 27 (41 mg, 42%) as a solid. M.p.:
ꢂ
1
2
47 C. H NMR (300 MHz, CDCl ) ꢀ: 8.31 (1H, dd, J ¼ 7.3, 1.0 Hz),
3

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134
Lee and Kim
8
.27–8.20 (2H, m), 7.82–7.42 (2H, m), 7.70 (1H, d, J ¼ 8.3 Hz), 7.58 (1H,
ddd, J ¼ 8.3, 7.3, 1.4 Hz), 7.50 (1H, ddd, J ¼ 8.2, 7.4, 1.0 Hz). IR (KBr):
3
1
079, 2963, 1667, 1593, 1578, 1566, 1487, 1445, 1372, 1325, 1225, 1182,
ꢀ
1
040, 1011, 990, 914, 874 cm
-Methylbenzo[b]naphtha[2,3-d ]furan-6,11-dione (28). Reaction of 22
100 mg, 0.4 mmol) with Pd/C (100 mg, 10 wt%) at reflux for 5 h in phenyl
.
2
(
ꢂ
1
ether (5 mL) afforded 28 (39 mg, 40%) as a solid. M.p.: 210 C. H NMR
300 MHz, CDCl ) ꢀ: 8.25–8.22 (2H, m), 8.10 (1H, s), 7.78–7.73 (2H, m),
(
3
7
1
.54 (1H, d, J ¼ 8.8 Hz), 7.38 (1H, d, J ¼ 8.8 Hz). IR (KBr): 2963, 1672,
ꢀ1
591, 1576, 1562, 1483, 1354, 1238, 1188, 1040, 1005, 937, 820 cm
Benzo[b]naphtha[2,1-d ]furan-5,6-dione (29). Reaction of 24 (95 mg,
.
0
.4 mmol) with Pd/C (95 mg, 10 wt%) at reflux for 5 h in phenyl ether
ꢂ
1
5 mL) afforded 29 (35 mg, 40%) as a solid. M.p.: 197–199 C. H NMR
(
(
7
300 MHz, CDCl ) ꢀ: 8.15–8.01 (2H, m), 7.92 (1H, dd, J ¼ 7.7, 1.0 Hz),
3
.71 (1H, ddd, J ¼ 7.7, 7.6, 1.0 Hz), 7.60–7.53 (2H, m), 7.43–7.37 (2H, m).
IR (KBr): 2928, 1701, 1674, 1644, 1584, 1557, 1485, 1441, 1408, 1356,
1
ꢀ
1
215, 1130, 1074, 909, 882 cm .
REFERENCES
1
. (a) Trani, A.; Dallanoce, C.; Panzone, G.; Ripamonti, F.; Goldstein,
B.P.; Ciabatti, R. J. Med. Chem. 1997, 40, 967; (b) Sendl, A.; Chen,
J.L.; Jolad, S.D.; Stoddart, C.; Rozhon, E.; Kernan, M. J. Nat. Prod.
1
996, 59. 808; (c) Gafner, S.; Wolfender, J.-L.; Nianga, M.;
Stoeckli-Evans, H.; Hostettmann, K. Phytochemistry 1996, 42,
315; (d) King, R.R.; Lawrence, H.; Calhoun, L.A. J. Agric. Food
1
Chem. 1996, 44, 2849; (e) Komiyama, K.; Funayama, S.; Anraku, Y.;
Ishibashi, M.; Takahashi, Y.; Omura, S. J. Antibiot. 1990, 43, 247; (f)
Hayashi, T.; Smith, F.T.; Lee, K.-H. J. Med. Chem. 1987, 30, 2005;
(
g) Inoue, K.; Ueda, S.; Nayeshiro, H.; Inouye, H. Chem. Pharm.
Bull. 1982, 30, 2265; (h) Inoue, K.; Chen, C.-C.; Inouye, H.;
Kuriyama, K. J. Chem. Soc., Perkin Trans. 1 1981, 2764; (i) Inouye, H.;
Ueda, S.; Inoue, K.; Shiobara, Y. Phytochemistry 1981, 20, 1707.
. (a) Kingston, L.A.; Rao, M.M. Planta Med. 1980, 39, 230;
2
3
4
(
b) Rao, M.M.; Kingston, D.G.I. J. Nat. Prod. 1982, 45, 600.
. Heltzel, C.E.; Leslie Gunatilaka, A.A.; Glass, T.E.; Kingston, D.G.I.
J. Nat. Prod. 1993, 56, 1500.
. Ribeiro-Rodrigues, R.; dos Santos, W.G.; Oliverira, A.B.;
Snieckus, V.; Zani, C.L.; Romanha, A.J. Bioorg. Medicinal Chem.
Letter 1995, 5, 1509.

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Dihydrofuranonaphthoquinones
4135
5
6
. Abbott, B.J.; Hartwell, J.L.; Leiter, J.; Perdue, R.E.; Schepartz, S.A.
Cancer Res. (Suppl.) 1967, 27, 190.
. (a) Cheng, C.C. Structural aspects of antineoplastic agents—a new
approach. In Progress of Medicinal Chemistry, Ellis, G.P., West,
G.B., Eds.; Elsevier Science Publishers, B. V. (Biomedical
Division): Amsterdam, 1988; Vol. 25, 35–83; (b) Cheng, C.C.;
Dong, Q.; Liu, D.-F.; Luo, Y.-I.; Liu, L.F.; Chen, A.Y.; Yu, C.;
Savaraj, N.; Chou, T.-C. J. Med. Chem. 1993, 36, 4108.
7. (a) Martınez, E.; Martınez, L.; Estevez, J.C.; Estevez, R.J.;
´ ´ ´ ´
Castedo, L. Tetrahedron Lett. 1998, 39, 2175; (b) Yoshida, K.;
Adachi, T.; Oga, N.; Kubo, Y. Chem. Lett. 1990, 2049; (c)
Yoshida, K.; Yamanaka, Y.; Ueno, Y. Chem. Lett. 1994, 2051.
. Lee, Y.R.; Kim, B.S.; Kim, D.H. Tetrahedron 2000, 56, 8845.
. Roy, S.C.; Mandal, P.K. Tetrahedron 1996, 52, 2193.
8
9
Received in Poland March 13, 2003

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